| First Author | Sugihara R | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 4494 |
| PubMed ID | 37524709 | Mgi Jnum | J:355453 |
| Mgi Id | MGI:7515789 | Doi | 10.1038/s41467-023-40201-4 |
| Citation | Sugihara R, et al. (2023) Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34. Nat Commun 14(1):4494 |
| abstractText | Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A(2)beta (iPLA(2)beta) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA(2)beta induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA(2)beta-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA(2)beta-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA(2)beta-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA(2)beta-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload. |
